Abstract:

The analgesic properties of L-tryptophan and 5-HTP can be safely enhanced
with the coadministration of salacin. Salacin can be effectively provided
in the form of white willow bark along with other ingredients to further
enhance the formulation's analgesic effect. As salacin can cause the loss
of vitamin C in humans, the formulation advantageously includes a
supplemental amount of vitamin C.

Claims:

1. A analgesic formulation comprising:salacin;at least one of L-tryptophan
and 5-HTP;niacinamide;pyridoxine;fructose; andvitamin C.

2. The formulation of claim 1, wherein said salicin is provided in the
form of at least one of white willow bark and extracts of white willow
bark.

3. The formulation of claim 1, wherein said salicin comprises up to about
500 mg of salacin.

4. The formulation of claim 1, wherein said at least one of said
L-tryptophan and 5-HTP comprises up to about 250 mg of said at least one
of said L-tryptophan and 5-HTP.

5. The formulation of claim 1, wherein said niacinamide comprises up to
about 25 mg of at least one of niacin and nicotinamide.

6. The formulation of claim 1, wherein said pyridoxine comprises up to
about 25 mg of pyridoxine.

7. The formulation of claim 1, wherein said fructore comprises up to about
25 mg of fructose.

8. The formulation of claim 1, wherein said vitamin C comprises up to
about 100 mg. of vitamin C.

9. The formulation of claim 1, further comprising zinc.

10. An analgesic formulation, comprising:up to about 500 mg salacin;up to
about 250 mg L-tryptophan;up to about 25 mg niacinamide;up to about 25 mg
pyridoxine;up to about 25 mg fructose; andup to about 500 mg vitamin C.

11. The formulation of claim 10, further comprising up to 24 mg of zinc.

12. The formulation of claim 10, wherein said salacin comprises about 250
mg of salacin.

13. The formulation of claim 10, wherein said salacin is provided in the
form of white willow bark.

14. The formulation of claim 10, wherein said L-tryptophan comprises about
100 mg of L-tryptophan.

15. The formulation of claim 10, wherein said niacinamide comprises about
10 mg of niacin.

16. The formulation of claim 10, wherein said fructose comprises about 25
mg of fructose.

18. The formulation of claim 11, wherein said zinc is provided in the form
of about 100 mg of zinc gluconate.

19. A method of relieving pain in a human, comprising:orally administering
to the human a formulation comprising salacin, at least one of
L-tryptophan and 5-HTP, niacinamide, pyridoxine, fructose and vitamin C.

20. The method of claim 19, wherein said salacin is administered in the
form of at least one of white willow bark and extracts of white willow
bark.

[0002]Intractable chronic pain can be eliminated or relieved through
administration of a formulation including L-tryptophan in combination
with the additional ingredients fructose, pyridoxine and niacinamide.
Each additional ingredient either promotes the transport of L-tryptophan
from the blood plasma across the blood-brain barrier into the brain or
promotes the conversion of L-tryptophan within the brain to the
neurotransmitter serotonin.

[0003]The production of the neurotransmitter serotonin can also be
increased through administration of a therapeutic composition which
includes L-tryptophan in combination with a salicylate, pyridoxine,
niacin and a carbohydrate such as fructose. Both the absolute free
fraction and the relative amount of the albumin-bound fraction of serum
L-tryptophan are increased so that transport of L-tryptophan from the
blood plasma across the blood-brain barrier into the brain is increased.
Once within the brain, L-tryptophan is converted to serotonin which
promotes pain relief and provides other beneficial effects.

[0004]The ability to proceed to market with a product incorporating a
salicylate like aspirin has been impeded due to the need and cost for
what is known as a New Drug Application or NDA. Previously, work to
proceed with a product based upon L-tryptophan was impeded by the Food
and Drug Administration (FDA) findings of a contaminant in L-tryptophan
that caused myalgias and death. It therefore was once desirable to avoid
the use of aspirin and L-tryptophan type compounds in order to expedite
market entry of a safe and effective analgesic.

[0005]L-tryptophan has now become once again commercially and economically
available and may now be used in dietary formulations including pain
relief formulations.

[0006]Alternatives to analgesics which require an NDA include herbal
formulations which generally do not require an NDA. One example of an
herbal analgesic is found in U.S. Pat. No. 6,312,736 which discloses an
herbal composition used to relieve pain and other symptoms associated
with migraines and other types of headaches. This herbal composition can
include white willow bark extract, kava kava root extract, feverfew
extract, ginger root extract, guarana extract, and vitamin B6. The herbal
composition may be combined with liposomes to carry the composition. The
result is an herbal composition that can be applied sublingually for pain
relief. This formulation is significantly different from the formulations
disclosed below in accordance with the subject disclosure.

SUMMARY

[0007]The present disclosure is directed to the use of willow bark to
increase the analgesic effect of L-tryptophan and 5-HTP. Although willow
bark has been used for pain relief, there are no known formulations for
increasing the production of serotonin by replacing a salicylate such as
aspirin with willow bark. It is believed that such replacement causes
several major beneficial factors to occur that have previously gone
unrecognized. The first is that willow bark in combination with other
pain relievers can enhance an analgesic effect in humans. Second, the use
of willow bark enables the introduction to the market of a safer
alternative than aspirin without negative gastro-intestinal effects.
Third, no advance in the formulation of pain relievers as proposed herein
has been located in the market or in the literature wherein willow bark
or its pain relieving component salacin have been combined with other
ingredients to promote the production of serotonin and the enhanced
relief of pain.

[0008]Ingestion of salacin causes a release of tryptophan from its binding
site on serum albumin and results in the presence of a free, unbound
fraction of L-tryptophan within the blood. This free fraction of
L-tryptophan is believed to control the concentration of L-tryptophan in
the brain, thereby increasing the brain's production of serotonin.

[0009]Instead of L-tryptophan, 5-hydroxytryptophan or "5-HTP" can also be
used as a safe alternative to L-tryptophan or in comination with
L-tryptophan. That is, 5-hydroxytryptophan or 5-HTP is a
naturally-occurring amino acid, a precursor to the neurotransmitter
serotin and an intermediate in tryptophan metabolism. It is marketed in
the United States and other countries as a dietary supplement for use as
an antidepressant, appetite suppressant, and sleep aid. As described
below, white willow bark, its pain relieving component salacin, as well
as other herbs, can be used to enhance the pain-relieving effects of
5-HTP. L-tryptophan, however, is acceptable as an alternative to 5-HTP or
in combination with 5-HTP for use as a pain reliever when combined with
any of the ingredients and formulations described below.

DESCRIPTION OF REPRESENTATIVE EMBODIMENTS

[0010]White willow bark, also known as salix alba, white willow, and
willow bark is a tree native to Europe and Asia. The name "white willow"
comes from the color of the leaves, which are covered with fine white
hairs. The use of white willow bark medicinally goes back to the ancient
Egyptians who used white willow to treat inflammation. The Greek
physician Hippocrates wrote about white willow's medicinal uses in the
5th century B.C.

[0011]In 1829, scientists in Europe identified what was believed to be the
active ingredient in white willow bark--a compound called salicin,
although other anti-inflammatory constituents also are present in white
willow bark. Public demand grew rapidly for salacin.

[0012]Extracting salicin from herbs was considered to be expensive and
time-consuming, so a synthetic salicylic acid version was developed in
Germany in 1852 and quickly became the treatment of choice. Salicin is
converted in the body to salicylic acid.

[0013]The problem was that salicylic acid is harder on the stomach than
salicin. At therapeutic doses, people using the synthetic salicyclic acid
developed stomach ulcers and bleeding.

[0014]The German company Bayer eventually created a synthetic, less harsh,
derivative of salicylic acid called acetylsalicylic acid (ASA), and
mass-produced it under the name aspirin. Despite this, aspirin is still
known for irritating the stomach lining. Replacing aspirin with salacin
can alleviate this problem.

[0015]Additional herbs, as identified below, can be combined with a
formulation of L-tryptophan, and/or 5-HTP and one or more of niacin or
nicotinamide, pyridoxine, fructose, vitamin C and white willow bark
(salacin) to achieve enhanced pain relief in a safe, "easy on the
stomach", oral capsule or other formulation. While these additional herbs
are associated with relief or treatment of certain maladies, any of the
following combinations of herbs can be used in combination with a base
formulation of L-tryptophan and/or 5-HTP, niacin or nicotinamide,
pyridoxine, fructose, vitamin C and white willow bark or any extract of
white willow bark.

[0016]For example, cramps and spasms can be treated with angelica, cramp
bar, kava, rosemary, and/or valerian root. Nerve pain can be treated with
capsaicin, chamomile, gotu kola, licorice, and white willow. Back pain
can be treated with hops, wood betony, and/or passionflower. Migraines
can be treated with feverfew, linden, and/or skullcap and headaches can
be treated with peppermint and/or spearmint. Any of these herbs can be
used with the base formulation described below.

[0017]Other herbs that are also useful in pain relief and which can be
combined with one or more of L-tryptophan and/or 5-HTP, niacin or
nicotinamide, pyridoxine, fructose, vitamin C and white willow bark (the
"base formulation") are set forth below.

[0018]Hot peppers such as cayenne pepper (capsilum) triggers the release
of the body's own pain-relieving endorphins and also includes
salicylates.

[0019]Cramp bark and black haw can be used for the treatment of spasmodic
pain. Both cramp bark (Viburnum opulus) and black haw (Viburnum
prunifolium) can be used to treat both menstrual pain, muscle spasm and
arthritic pain. These plants contain the antispasmodic and
muscle-relaxing compounds esouletin and scopoletin. These antispasmodic
constituents are best extracted with alcohol, so tinctures rather than
teas should be used. Black haw also contains aspirin-like compounds.
Equal parts of cramp bark and black haw tinctures in amounts between 1
and 4 droppers every two or three hours can be taken for up to three days
in combination with the subject L-tryptophan and/or 5-HTP base
formulation.

[0020]Menthol and camphor can be added to the base formulation to help
ease the muscle tightness that contributes to many back pains. Menthol is
a natural constituent of plants in the mint family, particularly
peppermint (menthe piperita) and spearmint, although the aromatic oils of
other mints contain menthol as well. Camphor occurs in spike lavender,
hyssop and coriander.

[0021]Ginger can be added to the base formulation to treat various sorts
of pain. Ginger contains 12 different aromatic anti-inflammatory
compounds, including some with mild aspirin-like effects. A fresh ginger
root (about the size of a thumb) can be cut into thin slices and placed
in a quart of water. The water is then brought to a boil, and then
simmered on the lowest possible heat for thirty minutes in a covered pot,
then cooled for thirty more minutes and then strained. About 1/2 to 1 cup
of the strained liquid is then taken orally along with the base
formulation.

[0022]Rosemary can also be added to the subject base formulation. Drinking
rosemary tea for pain is a known remedy. Rosemary leaf contains
anti-inflammatory substances including camosol, oleanolic acid,
rosmarinic acid, and ursolic acid. Carnosol acts on the same
anti-inflammatory pathways as both steroids and aspirin. Rosmarinic acid
acts through at least two separate anti-inflammatory biochemical pathways
and ursolic acid, which makes up about 4 percent of the plant by weight,
has been shown in animal trials to have anti-arthritic effects.

[0023]Epsom salt is reputed to have healing properties. Epsom salt is
primarily magnesium sulfate. The heat of an Epsom salt bath can increase
circulation and reduce the swelling of arthritis, and the magnesium can
be absorbed through the skin. Magnesium is one of the most important
minerals in the body, participating in at least 300 enzyme systems.
Magnesium has both anti-inflammatory and anti-arthritic properties.
Taking an external Epsom salt bath while also ingesting the base
formulation can provide an enhanced analgesic effect.

[0025]A therapeutic composition comprising oregano oil, laurel oil, and
myrtle oil useful in alleviating pain and discomfort associated with
arthritis, migraines, bronchitis, soft tissue injuries, muscle aches and
pains and neck and back pains and strains in humans, as well as upper
respiratory, joint and shin ailments in animals can also be added to the
subject base formulation.

[0026]An externally applicable analgesic composition including an extract
derived from sumac leaves, sassafrass root, oak tree bark and an alcohol
component, combined with benzocaine, procaine and menthol components can
supplement the oral administration (ingestion) of subject base
formulation. The topical application of this composition has proven
effective for the temporary relief of pain and stiffness associated with
arthritis, bursitis, muscle cramp and other aches and pains.

[0027]Also disclosed for pain are compositions containing either aspartame
or monosodium glutanate combined with an amino acid and added to the base
formulation.

[0028]Those familiar with the art may find ways to incorporate any one or
more of the herbs mentioned above into the subject base formulation
including 5-HTP or L-tryptophan and/or any one or more of niacinamide,
pyridoxine, fructose, vitamin C and willow bark or salicin. An oral
capsule of such a formulation is one desired form of administration.

[0029]Fructose is included in each capsule as a preferred source of
carbohydrate to achieve insulin/LNAA/tryptophan effect. That is, not only
is tryptophan and 5-HTP carried by this transport mechanism, but other
selected amino acids, called large electrically neutral amino acids
(LNAA's) are carried across the blood-brain barrier as well.

[0030]A lowered pain threshold is enabled with L-tryptophan or 5-HTP being
able to pass the blood brain barrier in combination with fructose, niacin
and pyridoxine (vitamin B-6) thereby effectively increasing serotonin and
enhancing the analgesic effectiveness of the salicin derived from willow
bark.

[0031]Since willow bark and salicylates such as aspirin can also cause the
loss of vitamin C, another important focus of the formulation is to
include vitamin C or ascorbic acid as a component of the base formulation
in an amount from 50 mg to 500 mg. to replace any vitamin C or ascorbic
acid loss caused by ingestion of salacin and/or willow bark.

[0032]Since analgesics are commonly used to treat cold and flu symptoms,
and it is known that 9 to 24 mg. of elemental zinc may add certain
benefits, the use of zinc such as in the form of a zinc salt such as zinc
gluconate may also be added to the base formulation for effectively
treating cold and flu symptoms.

EXAMPLE

[0033]While the weight of each ingredient listed below could vary up to
approximately 50% more, the base formulation for an effective analgesic
single dosage for a typical human patient is as follows:

[0034](1) L-tryptophan or 5-HTP or a combination thereof, up to about 250
mg; (2) niacinamide (niacin or nicotinamide), a natural vitamin, up to
about 25 mg; (3) pyridoxine (vitamin B6), a natural vitamin, up to about
25 mg; (4) fructose, a natural sugar, up to about 25 mg, (5) salicin,
such as provided in willow bark (white willow bark) in an amount
sufficient to provide up to about 500 mg of salicin and vitamin C in an
amount up to about 500 mg.

[0035]Another example of an effective analgesic formulation is set forth
below, with the weight of each ingredient variable within a range of plus
or minus 50%, as broadened and defined by the term "about". Zinc
gluconate is optional.

[0036]In the examples, salacin can be provided in the form of (white)
willow bark extract. Such an extract is commercially available with the
concentration of salacin ranging from 15% to 95% by weight. The
concentration of salacin in extracts is not particularly critical as long
as the prescribed weight of salacin is administered to one in need of
pain relief.

[0037]While the base formulation is susceptible to alternative
constructions, certain embodiments thereof have been described above in
detail. It should be understood, however, that there is no intention to
limit the disclosure to the specific form or embodiments disclosed, but
on the contrary, the intention is to cover all modifications, alternative
constructions, and equivalents falling within the spirit and scope of the
disclosure.

[0038]For example, the claimed formulation may be in the form of powders,
tablets, capsules, lozenges, and bicarbonated versions to produce a
seltzer drink, a ready to use liquid form in water or other palatable
medium or topical gel or cream. As used in the claims, the term "about"
means a variance of fifty percent (50%).